Hematologic effects of a novel hemoglobin-based oxygen carrier in normal male and female subjects.

The objective of this study was to assess the relationship between iron metabolism and pharmacokinetics of hemoglobin-based oxygen carrier-201 (HBOC-201), a polymerized hemoglobin product of bovine origin. A randomized, single-blind, single-dose study design was used. The study was performed at the Upjohn Research Clinics in Kalamazoo, Michigan. Four groups of healthy men and women (n = 24), who either received HBOC-201 (9 men, 9 women) or a control solution (Ringer's lactate) (3 men, 3 women) participated in the study. All subjects had phlebotomy (approximately 15% blood volume) followed by 3:1 hemodilution with Ringer's lactate and an intravenous infusion of HBOC-201 (up to 45 gm or 350 ml) or control solution (Ringer's lactate). Serial arterial blood gas samples with a radial artery catheter and simultaneous pulse oximetry were done during the first 24 hours. Serial samples for serum iron, ferritin, erythropoietin, and plasma HBOC-201 levels were taken over a 1-month period. In the HBOC-201-treated groups, serum iron and ferritin levels increased. Peak serum iron and ferritin levels occurred by hours 8 (up to 220 micrograms/dl) and 48 (up to 180 ng/ml), respectively. Serum iron levels paralleled HBOC-201 concentrations. Plasma half-life of HBOC-201 was about 20 hours. Serum erythropoietin increased by twofold to sixfold over baseline (p < 0.001) at 24 hours. No urinary hemoglobin was detected in the groups with HBOC-201-treated subjects. This study demonstrates that HBOC-201 produces increases in serum iron, ferritin, and erythropoietin that closely parallel plasma levels of HBOC-201 in men and women.

RCT Entities:   Population Interventions Outcomes